For Release on Delivery

Expected at 10:00 a.m.

Thursday, September 28, 2000

GAO/T-HEHS-00-203

VA RESEARCH

System for Protecting

Human Subjects Needs

Improvements

Statement of Victor S. Rezendes, Assistant Comptroller General

Health, Education, and Human Services Division

Testimony

Before the Subcommittee on Oversight & Investigations,

Committee on Veterans' Affairs, House of Representatives

United States General Accounting Office

GAO
Page 1 GAO/T-HEHS-00-203

Mr. Chairman and Members of the Subcommittee:

I am pleased to be here to discuss the report we are issuing today to you

and other requesters on the Department of Veterans Affairs (VA) system

for protecting the rights and welfare of veterans who volunteer to

participate in research at VA medical centers.1 It has been 18 months since

research was suspended at the West Los Angeles VA Medical Center2

because officials failed to correct longstanding problems in its human

subject protection system. Since that suspension, four additional VA

medical centers have felt the repercussions of sanctions by regulatory

agencies against their affiliated universities. My testimony summarizes our

assessment of VA’s implementation of human subject protections,

highlights systemwide weaknesses we identified in those protections, and

evaluates VA’s actions to better protect human subjects at medical centers

that have been affected by sanctions and throughout VA’s healthcare

system.

Based on our review of eight medical centers, we concluded that VA needs

to take action to strengthen the protection of human research subjects.

Although the extent of the problems was uneven, we documented a

disturbing pattern of noncompliance across the centers we visited. The

cumulative weight of the evidence indicated failures to consistently

safeguard the rights and welfare of research subjects. We also identified

three specific weaknesses that have compromised VA’s ability to protect

human subjects—lack of adequate guidance to medical centers about

human subject protections, insufficient monitoring of local protections,

and inadequate attention to ensuring that funds needed for human subject

protection activities are allocated and available for those purposes. To

VA’s credit, at three other medical centers we visited, substantial

corrective actions have been implemented in response to sanctions by

regulatory agencies taken against their human research programs. In

contrast, VA’s systemwide efforts at improving protections have been slow

to develop.

Conducting medical research is one of VA’s core missions. VA researchers

have been involved in a variety of important advances in medical research,

including development of the cardiac pacemaker, kidney transplant

1VA Research: Protections for Human Subjects Need to Be Strengthened (GAO/HEHS-00-155, Sept. 28,

2000).

2 The West Los Angeles VA Medical Center is now part of the VA Greater Los Angeles Healthcare

System.

VA Research: System for Protecting Human

Subjects Needs Improvement

Background
VA Research: System for Protecting Human

Subjects Needs Improvement

Page 2 GAO/T-HEHS-00-203

technology, prosthetic devices, and drug treatments for high blood

pressure and schizophrenia. Funds from the appropriations for VA medical

research and VA medical care support VA researchers and the indirect

costs of research, which includes support for the human subject

protection system. VA researchers receive additional grants and contracts

from other federal agencies such as the National Institutes of Health

(NIH), research foundations, and private industry sponsors including

pharmaceutical companies. In fiscal year 2000, biomedical or behavioral

research involving human subjects is being conducted at about 70 percent

of VA medical centers.

VA is responsible for ensuring that all human research it conducts or

supports meets the requirements of VA regulations, regardless of whether

that research is funded by VA, the subjects are veterans, or the studies are

conducted on VA grounds. Responsibility for administration and oversight

of the research program has rested primarily with the Office of Research

and Development (ORD). Recently, VA created the Office of Research

Compliance and Assurance (ORCA) to advise the Under Secretary for

Health on matters affecting the integrity of research protections, to

promote the ethical conduct of research, and to investigate allegations of

research impropriety. In addition, some VA research is subject to oversight

by two components of the Department of Health and Human Services

(HHS). The Food and Drug Administration (FDA) is responsible for

protecting the rights of human subjects enrolled in research with products

it regulates—drugs, medical devices, biologics, foods, and cosmetics. HHSfunded research is subject to oversight by its Office for Human Research

Protections (OHRP).3

Research offers the possibility of benefits to individuals or to society, but

it is not without risk to research subjects. To protect the rights and welfare

of human research subjects, 17 federal departments and agencies,

including VA, adopted regulations designed to safeguard the rights of

subjects and promote ethical research. These regulations establish

minimum standards for the conduct and review of research to ensure that

studies are conducted in accordance with the ethical principles outlined in

the Belmont Report, issued by the National Commission for the Protection

of Human Subjects of Biomedical and Behavioral Research. These

principles require that subjects voluntarily give informed consent to

3The Office for Human Research Protections (OHRP) is in the Office of the Assistant Secretary for

Health. HHS established OHRP in June 2000 to assume the human subject protection functions of the

former Office for Protection from Research Risks (OPRR), which was part of NIH. We refer to both

organizations as OHRP. Actions taken before June 18, 2000, were taken by OPRR.
VA Research: System for Protecting Human

Subjects Needs Improvement

Page 3 GAO/T-HEHS-00-203

participate in research and that the expected benefits of research to the

individual or to society outweigh its anticipated risks.

Federal regulations create a system in which the responsibility for

protecting human subjects is assigned to three groups. Investigators are

responsible for conducting research in accordance with regulations.

Institutions are responsible for establishing oversight mechanisms for

research, including local committees known as institutional review boards

(IRB) that are responsible for reviewing both research proposals and

ongoing research. Agencies, including VA, are responsible for ensuring

that their IRBs comply with applicable federal regulations and have

sufficient space and staff to accomplish their obligations. VA requires that

each of its medical centers engaged in research with human subjects

establish its own IRB or secure the services of an IRB at an affiliated

university. As of August 2000, approximately 40 percent of the VA medical

centers conducting research with human subjects relied on an IRB at an

affiliated university.

We found various degrees of noncompliance with VA regulations and

policies involving protections for human subjects at the eight medical

centers we visited. Although we recognize that the results of our visits

cannot be projected to VA as a whole, we found sufficient patterns of

noncompliance to be concerned. We saw multiple problems at some sites,

but relatively fewer problems at others. The five sites we visited that relied

on VA-run IRBs had the most extensive problems. The three university-run

IRBs we visited, however, were not without problems.

We found that medical centers and their affiliated universities did not

comply with all the regulations designed to protect the rights and welfare

of research participants in four areas: (1) informed consent; (2) IRB

review; (3) IRB membership, staff, and space; and (4) IRB documentation.

OHRP noted similar compliance problems in letters to universities and

hospitals it has found to be out of compliance with federal regulations. As

shown in fig. 1, some sites we visited had more problems than others.

Implementation of

Human Subject

Protections Uneven
VA Research: System for Protecting Human

Subjects Needs Improvement

Page 4 GAO/T-HEHS-00-203

Figure 1: Noncompliance with VA Regulations at Eight Sites

a

We reviewed from 14 to 20 IRB-approved consent forms at each site, for a total of 138

forms.
VA Research: System for Protecting Human

Subjects Needs Improvement

Page 5 GAO/T-HEHS-00-203

b

We compared consent forms signed by subjects to IRB-approved consent forms for 17 to

20 studies at each of 4 sites. We compared forms for a total of 73 studies.

We found problems with the content or use of informed consent forms at

all of the medical centers we visited. We found that some informed

consent documents that had been approved for use by IRBs provided

incomplete or unclear information. For example, we found that a consent

form given to subjects did not mention possible risks of a biopsy in a study

designed to test a treatment for esophageal cancer. We found another that

did not indicate who would have access to data obtained during a study on

treatment for cirrhosis of the liver. We found a third that did not describe

alternative treatment options in a study comparing two drug treatments

for schizophrenia. Obtaining informed consent is a primary ethical

requirement of research with human subjects. The ability of competent

subjects to make their own informed decisions about whether to

participate in research and the ability of legally authorized representatives

to protect those unable to provide consent because they are incapacitated

are undermined when IRBs fail to ensure that all required information is

included in consent forms or when investigators fail to obtain consent

using approved procedures.

We also found that five of the sites we visited did not implement certain

required procedures for IRB review of research. For example, one IRB

held meetings without having all required members in attendance. Studies,

such as those on new drug treatments for unstable coronary symptoms

and pneumonia, were thus initiated without legitimate approval. In

addition, three review boards did not meet the requirement that each

study be re-reviewed at least once a year. At one of these, a VA-run IRB, rereview delays of up to 14 months occurred in one-half of the projects we

sampled. Regular re-review allows reassessment of a study’s ratio of risks

to benefits in light of data obtained since a study was begun, such as data

about adverse events.

We found problems with IRB membership, staff, and space. Two IRBs we

visited did not ensure that their members had no potential conflict of

interest, four IRBs did not have adequate staff to support review activities,

and IRB staff at three sites did not have sufficient space to conduct their

work or store all necessary documents. IRBs must have secure, private

areas for the review, discussion, and storage of confidential materials. But

we observed IRB file folders stacked loosely on top of filing cabinets and

on floors at one of these sites.

In addition, six of the eight IRBs we visited did not maintain all the records

required by VA regulations. We found incomplete documentation of IRB

activities, such as local written IRB procedures that were inadequate, IRB
VA Research: System for Protecting Human

Subjects Needs Improvement

Page 6 GAO/T-HEHS-00-203

meeting minutes that did not document substantive discussions, and votes

that were improperly recorded. One medical center we visited had been

cited by the FDA in June 1999 for failure to have adequate written

procedures. The center agreed to have them in place by August 1999 but

did not do so until December 1999. The written procedures we reviewed

from three other VA-run IRBs did not include required descriptions of

procedures for conducting project review, determining when additional

project monitoring is necessary, or responding to investigator

noncompliance. Although inadequate documentation does not alone place

subjects at risk, documentary failures prevent appropriate monitoring and

oversight activities. For example, records of actions, deliberations, and

procedures can help identify problems and corrective actions.

We identified three specific weaknesses in VA’s system for protecting

human subjects: not ensuring that research staff have appropriate

guidance, insufficient monitoring and oversight activity, and not ensuring

that the necessary funds for human subject protection activities are

provided. These weaknesses indicate that human subject protection issues

have not historically received adequate attention from VA headquarters.

VA headquarters had not provided medical center research staff with

adequate guidance about human subject protections and thus had not

ensured that research staff had all the information they need to protect the

rights and welfare of human subjects. We found that VA had not developed

a systemwide educational program or ensured that each of its facilities

had an appropriate training program in place. A need for increased

educational guidance from headquarters was one of the most commonly

identified issues regarding human subject protections in a VA-sponsored

survey of network managers. Educational programs are critical to

ensuring that IRBs and investigators can implement appropriate

protection for human research subjects.

The second weakness we identified is that VA did not have an effective

system for monitoring protections of subjects, thus allowing

noncompliance with regulations to go undetected and uncorrected. For

example, we found that VA headquarters and affected medical centers

were generally unaware of regulatory investigations and impending

actions by OHRP and FDA against university-run IRBs until after the

regulatory sanctions were applied. Also, VA headquarters has not provided

medical centers with guidance on ensuring access to minutes or other key

information when they arrange for the services of a university-run IRB. As

a result, one medical center we visited did not have access to the minutes

of its university-run IRB, and two medical centers affected by regulatory

Specific Weaknesses

Compromise VA’s

Protection of Human

Subjects
VA Research: System for Protecting Human

Subjects Needs Improvement

Page 7 GAO/T-HEHS-00-203

sanctions against their affiliated universities had not monitored IRB

minutes to assess compliance with regulations. Seven of the eight medical

centers we visited did not routinely check whether investigators provided

subjects with the correct IRB-approved consent form.

The third weakness we identified is that VA has not ensured that funds

needed for human subject protections are allocated for that purpose at the

medical centers. Officials at some medical centers told us that they did not

have sufficient resources to accomplish their mandated responsibilities.

We found that responsibility for funding human subject protections is

diffused across several decisionmakers: the medical center’s associate

chief of staff for research and development, the medical center’s director,

and the board of directors of the medical center’s nonprofit research

foundation, which has discretion over the use of funds from non-VA

research sponsors. Each of these may also have competing priorities for

the same funds. The result is that no one official is responsible for

ensuring that medical center research programs have the resources they

need to support IRB operations and provide training in human subject

protections. Research officials at five of the eight medical centers we

visited reported that they had insufficient funds to ensure adequate

operation of their human subject protection systems. Moreover,

headquarters research officials told us that VA has not determined the

funding needed for human subject protection activities at the medical

centers.

To VA’s credit, substantial corrective actions have been implemented at

three medical centers we visited in response to regulatory sanctions taken

against their human research programs. However, VA’s systemwide efforts

to improve protections have been slow to develop.

Medical centers and affiliated universities affected by sanctions have

taken numerous steps to improve human subject protections. They have,

for example, hired and trained IRB staff and developed written procedures

for their IRB operations. These medical centers and affiliated universities

have made progress, and each has resumed human research activities.

We identified several issues of concern at some of these medical centers,

however. For example, VA’s authorization of a resumption of IRB

operations at the West Los Angeles VA Medical Center on April 19, 1999—

less than 1 month after OHRP’s sanctions against the medical center—was

premature. At that time, the medical center still lacked approved, written

procedures for operation, relied on untrained administrative staff to assist

newly formed IRBs, and had not provided investigators with training in

Local Actions Address

Problems Identified

by Regulators but

Systemwide Focus

Slow to Develop
VA Research: System for Protecting Human

Subjects Needs Improvement

Page 8 GAO/T-HEHS-00-203

human subject protection issues. We are also concerned that officials at

the medical center were particularly slow to respond to the issues OHRP

identified over a 5-year period, including the requirement to establish a

data and safety monitoring board to oversee studies involving subjects

with severe psychiatric disorders.

VA also has been slow to identify systemwide deficiencies and obtain

necessary information about the human subject protection systems at its

medical centers. Although OHRP identified problems with human subject

protections at the West Los Angeles VA Medical Center in 1994, VA did not

have a plan to address systemwide concerns involving research until July

1998. VA did not begin to implement systemwide changes until after OHRP

took regulatory action against the medical center in March 1999.

Only recently has VA headquarters begun to implement systemwide

changes to improve its human subject protections. Its steps have included

providing information to investigators and research staff and obtaining

information about medical centers’ research programs, such as identifying

medical centers that use their own IRBs and those that use university-run

IRBS, which will allow headquarters officials to determine the additional

steps that may be needed locally or systemwide to ensure compliance with

regulations and protection of human subjects.

In addition, VA is making two organizational changes to enhance

monitoring and oversight of human research. The changes are designed to

allow routine onsite monitoring of medial centers’ research programs,

thereby helping medical centers identify weaknesses and develop

strategies to improve compliance with human subject protection

regulations. Although promising in concept, it is too soon to determine

whether these initiatives will fulfill their objectives. The first, the creation

of ORCA, was announced in April 1999, but VA did not appoint the chief

officer until December 1999. As of September 2000, staffing of ORCA,

which includes four regional offices, was incomplete. Although ORCA’s

specific plans for monitoring medical center research activities are still

under development, ORCA officials told us they planned to conduct a site

visit to each medical center on a rotating basis. In its second initiative, VA

has awarded a contract for external accreditation of its IRBs. The

contractor is expected to conduct a site visit to each medical center

conducting research with human subjects every 3 years to review IRB

performance and assess compliance with regulations. VA officials told us

VA expects that the university-run IRBs it uses will grant access to the

accreditation team. VA is the first research organization to seek external

accreditation of its human research programs.
VA Research: System for Protecting Human

Subjects Needs Improvement

Page 9 GAO/T-HEHS-00-203

VA needs to do more systemwide to protect the rights and welfare of

human subjects who participate in research at VA medical centers. In the

report we issue today, we make recommendations to the Acting Secretary

of Veterans Affairs to take immediate steps to provide staff training and

resources and to take other measures to ensure that VA medical centers,

their IRBs—whether operated by VA or not—and VA investigators comply

with all applicable regulations for the protection of human subjects.

In concurring with the recommendations, VA identified the steps it has

taken and its planned initiatives. Critical to timely and effective

implementation will be sustained commitment to a program of heightened

vigilance regarding the protection of human subjects. Without this, the

rights and welfare of veterans who participate in VA research remain

vulnerable.

Mr. Chairman, this concludes my prepared statement. I will be happy to

answer any questions that you or Members of the Subcommittee may have.

For more information regarding this testimony, please contact Cynthia A.

Bascetta at (202) 512-7101. Key contributors to this testimony include

Bruce D. Layton, Cheryl Brand, and Kristen Joan Anderson.

(406206)

GAO Contact and

Staff

Acknowledgments
Orders by Internet

For information on how to access GAO reports on the Internet, send

an e-mail message with “info” in the body to:

Info@www.gao.gov

or visit GAO’s World Wide Web home page at:

http://www.gao.gov

Contact one:

Web site: http://www.gao.gov/fraudnet/fraudnet.htm

E-mail: fraudnet@gao.gov

1-800-424-5454 (automated answering system)

Ordering Information

To Report Fraud,

Waste, and Abuse in

Federal Programs